Exploration of the mechanism by which Huangqi Guizhi Wuwu decoction inhibits Lps-induced inflammation by regulating macrophage polarization based on network pharmacology.
Exploration of the mechanism by which Huangqi Guizhi Wuwu decoction inhibits Lps-induced inflammation by regulating macrophage polarization based on network pharmacology.
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基于网络药理学探讨黄芪桂枝五物汤通过调节巨噬细胞极化抑制Lps诱导炎症的机制
DOI：
10.1186/s12906-022-03826-4
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发表时间：
2023-01-09
影响因子：
3.9
通讯作者：
Jiang, Ping
中科院分区：
文献类型：
--
作者：
Wang, Sutong;Ji, Tianshu;Wang, Lin;Qu, Yiwei;Wang, Xinhui;Wang, Wenting;Lv, Mujie;Wang, Yongcheng;Li, Xiao;Jiang, Ping
黄芪桂枝五物汤（HQGZWWD）是一种具有显着抗炎活性的中草药制剂。然而，其根本机制仍不清楚。本研究旨在通过网络药理学和实验验证，探讨HQGZWWD调节巨噬细胞极化和炎症的潜在机制。活性成分从中药系统药理学数据库和分析平台（TCMSP）获得，相应的靶点从TCMSP和瑞士靶标预测数据库获得。 GeneCards 数据库确定了与巨噬细胞极化和炎症相关的靶标。开发了多个网络来识别 HQGZWWD 调节巨噬细胞极化和炎症的关键化合物、主要生物过程和途径。 Autodock Vina 用于评估靶标与活性化合物之间的结合能力。最后，验证实验的中心假设。人组织细胞淋巴瘤（U-937）细胞经脂多糖（LPS）刺激后转化为M1巨噬细胞，以评价HQGZWWD含药小鼠血清（HQGZWWD血清）调节巨噬细胞极化和炎症的作用。共获得54个活性成分和859个HQGZWWD目标。有 9972 个与巨噬细胞极化相关的靶点和 11,109 个与炎症相关的靶点。经过筛选，鉴定出34个重叠靶点，其中5个经实验证实为中心靶点，包括α7烟碱乙酰胆碱受体（α7 nAchR）、白细胞介素6（IL-6）、白细胞介素1β（IL-1β）、白细胞介素10（IL-10）和生长因子β（TGF-β1）。通路富集分析显示，34个重叠靶点在与巨噬细胞极化和炎症相关的多个通路中富集，包括TGFβ信号通路、NF-κB信号通路、JAK-STAT信号通路和TNF信号通路。分子对接证实HQGZWWD的大多数化合物可以与靶标结合。体外实验显示，HQGZWWD血清可上调α7 nAchR的表达，减少M1巨噬细胞的数量，刺激M2巨噬细胞的产生，抑制促炎细胞因子IL-6和IL1-β的表达，并增加抗炎细胞因子IL-10和TGF-β1的表达。 HQGZWWD能够调节M1/M2巨噬细胞的数量和炎性细胞因子的水平，其机制可能与上调α7 nAchR的表达有关。在线版本包含可在 10.1186/s12906-022-03826-4 获取的补充材料。
Huangqi Guizhi Wuwu decoction (HQGZWWD) is a traditional Chinese herbal medicine formulation with significant anti-inflammatory activity. However, its underlying mechanism remains unknown. Through network pharmacology and experimental validation, this study aimed to examine the potential mechanism of HQGZWWD in regulating macrophage polarization and inflammation. The active components were obtained from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP), whereas the corresponding targets were obtained from the TCMSP and Swiss Target Prediction database. The GeneCards database identified targets associated with macrophage polarization and inflammation. Multiple networks were developed to identify the key compounds, principal biological processes, and pathways of HQGZWWD that regulate macrophage polarization and inflammation. Autodock Vina is utilized to assess the binding ability between targets and active compounds. Finally, confirm the experiment’s central hypothesis. Human histiocytic lymphoma (U-937) cells were transformed into M1 macrophages following stimulation with Lipopolysaccharide (LPS) to evaluate the effect of HQGZWWD drug-containing mouse serum (HQGZWWD serum) on regulating macrophage polarization and inflammation. A total of 54 active components and 859 HQGZWWD targets were obtained. There were 9972 targets associated with macrophage polarization and 11,109 targets associated with inflammation. After screening, 34 overlapping targets were identified, of which 5 were identified as central targets confirmed by experiments, including the α7 nicotinic acetylcholine receptor (α7 nAchR), interleukin 6 (IL-6), Interleukin-1 beta (IL-1β), interleukin 10 (IL-10) and growth factor beta (TGF-β1). Pathway enrichment analysis revealed that 34 overlapping targets were enriched in multiple pathways associated with macrophage polarization and inflammation, including the TGF beta signaling pathway, NF-kappa B signaling pathway, JAK-STAT signaling pathway, and TNF signaling pathway. Molecular docking confirmed that the majority of HQGZWWD’s compounds can bind to the target. In vitro experiments, HQGZWWD serum was shown to up-regulate the expression of α7 nAchR, reduce the number of M1 macrophages, stimulate the production of M2 macrophages, inhibit the expression of pro-inflammatory cytokines IL-6 and IL1-β, and increase the expression of anti-inflammatory cytokines IL-10 and TGF-β1. HQGZWWD can regulate the number of M1/M2 macrophages and the level of inflammatory cytokines, and the underlying mechanism may be related to the up-regulation of α7 nAchR expression. The online version contains supplementary material available at 10.1186/s12906-022-03826-4.
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影响因子：
1.6
作者：
通讯作者：
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影响因子：
7.3
作者：
Fukui S;Iwamoto N;Takatani A;Igawa T;Shimizu T;Umeda M;Nishino A;Horai Y;Hirai Y;Koga T;Kawashiri SY;Tamai M;Ichinose K;Nakamura H;Origuchi T;Masuyama R;Kosai K;Yanagihara K;Kawakami A
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Kawakami A
影响因子：
9.3
作者：
De Simone R;Ajmone-Cat MA;Carnevale D;Minghetti L
通讯作者：
Minghetti L
影响因子：
50.3
作者：
Bai, Longchuan;Zhou, Haibin;Wang, Shaomeng
通讯作者：
Wang, Shaomeng
影响因子：
64.8
作者：
GHOSH, G;VANDUYNE, G;SIGLER, PB
通讯作者：
SIGLER, PB